Terry F. Hayamizu

Effects of localized application of transforming growth factor β1 on developing chick limbs

The effects of exogenous transforming growth factor beta (TGF-beta) on chick limb development in vivo were studied by implanting carriers of TGF-beta 1 into developing wing buds. Agarose beads were soaked in solutions containing TGF-beta 1 and implanted into wing buds at stages 18 to 27. Localized application of TGF-beta 1 to distal regions of the wing bud caused specific skeletal elements in the limb to be reduced or absent. The particular proximal-distal limb element affected depended on the stage at which the bead was implanted. Position of the bead in the anterior-posterior axis also influenced the pattern of affected structures. Experiments in which TGF-beta 1 beads were implanted and then removed at 24- and 48-hr intervals indicate that there are specific periods during which a skeletal element appears to be sensitive to the effects of exogenous TGF-beta 1. In a few cases, beads placed in proximal positions in later staged limbs resulted in formation of ectopic cartilage near the bead. These results suggest that exposure to exogenous TGF-beta 1 in vivo influences the development of skeletal elements in the chick limb in a stage- and position-dependent manner.

GXD: a community resource of mouse Gene Expression Data

The Gene Expression Database (GXD) is an extensive, easily searchable, and freely available database of mouse gene expression information (www.informatics.jax.org/expression.shtml). GXD was developed to foster progress toward understanding the molecular basis of human development and disease. GXD contains information about when and where genes are expressed in different tissues in the mouse, especially during the embryonic period. GXD collects different types of expression data from wild-type and mutant mice, including RNA in situ hybridization, immunohistochemistry, RT-PCR, and northern and western blot results. The GXD curators read the scientific literature and enter the expression data from those papers into the database. GXD also acquires expression data directly from researchers, including groups doing large-scale expression studies. GXD currently contains nearly 1.5xa0million expression results for over 13,900 genes. In addition, it has over 265,000 images of expression data, allowing users to retrieve the primary data and interpret it themselves. By being an integral part of the larger Mouse Genome Informatics (MGI) resource, GXD’s expression data are combined with other genetic, functional, phenotypic, and disease-oriented data. This allows GXD to provide tools for researchers to evaluate expression data in the larger context, search by a wide variety of biologically and biomedically relevant parameters, and discover new data connections to help in the design of new experiments. Thus, GXD can provide researchers with critical insights into the functions of genes and the molecular mechanisms of development, differentiation, and disease.

Mouse anatomy ontologies: enhancements and tools for exploring and integrating biomedical data

Mouse anatomy ontologies provide standard nomenclature for describing normal and mutant mouse anatomy, and are essential for the description and integration of data directly related to anatomy such as gene expression patterns. Building on our previous work on anatomical ontologies for the embryonic and adult mouse, we have recently developed a new and substantially revised anatomical ontology covering all life stages of the mouse. Anatomical terms are organized in complex hierarchies enabling multiple relationships between terms. Tissue classification as well as partonomic, developmental, and other types of relationships can be represented. Hierarchies for specific developmental stages can also be derived. The ontology forms the core of the eMouse Atlas Project (EMAP)xa0and is used extensively for annotating and integrating gene expression patterns and other data by the Gene Expression Databasexa0(GXD), the eMouse Atlas of Gene Expressionxa0(EMAGE) and other database resources. Here we illustrate the evolution of the developmental and adult mouse anatomical ontologies toward one combined system. We report on recent ontology enhancements, describe the current status, and discuss future plans for mouse anatomy ontology development and application in integrating data resources.

The mouse-human anatomy ontology mapping project.

The overall objective of the Mouse–Human Anatomy Project (MHAP) was to facilitate the mapping and harmonization of anatomical terms used for mouse and human models by Mouse Genome Informatics (MGI) and the National Cancer Institute (NCI). The anatomy resources designated for this study were the Adult Mouse Anatomy (MA) ontology and the set of anatomy concepts contained in the NCI Thesaurus (NCIt). Several methods and software tools were identified and evaluated, then used to conduct an in-depth comparative analysis of the anatomy ontologies. Matches between mouse and human anatomy terms were determined and validated, resulting in a highly curated set of mappings between the two ontologies that has been used by other resources. These mappings will enable linking of data from mouse and human. As the anatomy ontologies have been expanded and refined, the mappings have been updated accordingly. Insights are presented into the overall process of comparing and mapping between ontologies, which may prove useful for further comparative analyses and ontology mapping efforts, especially those involving anatomy ontologies. Finally, issues concerning further development of the ontologies, updates to the mapping files, and possible additional applications and significance were considered. Database URL: http://obofoundry.org/cgi-bin/detail.cgi?id=ma2ncit

Patterning in Limbs: The Resolution of Positional Confrontations

Positional confrontations are characteristic of the development of all multicellular organisms. In amphibian embryos, for example, formation of the mesoderm is dependent on contact between vegetal and animal pole cells (Symes et al. 1988). Later, mesodermal cells specified for dorsal and ventral fates interact to generate cells with intermediate fates (Dale & Slack 1987). In some insects, the trunk region develops from interactions between head and ‘tail’ structures (Cohen & Jurgens 1991). Finally, confrontations between differently-specified cells are required for limb outgrowth during development and regeneration (Bryant & Gardiner 1992).

The mouse gene expression database: New features and how to use them effectively.

The Gene Expression Database (GXD) is an extensive and freely available community resource of mouse developmental expression data. GXD curates and integrates expression data from the literature, via electronic data submissions, and by collaborations with large‐scale projects. As an integral component of the Mouse Genome Informatics Resource, GXD combines expression data with genetic, functional, phenotypic, and disease‐related data, and provides tools for the research community to search for and analyze expression data in this larger context. Recent enhancements include: an interactive browser to navigate the mouse developmental anatomy and find expression data for specific anatomical structures; the capability to search for expression data of genes located in specific genomic regions, supporting the identification of disease candidate genes; a summary displaying all the expression images that meet specified search criteria; interactive matrix views that provide overviews of spatio‐temporal expression patterns (Tissue × Stage Matrix) and enable the comparison of expression patterns between genes (Tissue × Gene Matrix); data zoom and filter utilities to iteratively refine summary displays and data sets; and gene‐based links to expression data from other model organisms, such as chicken, Xenopus, and zebrafish, fostering comparative expression analysis for species that are highly relevant for developmental research. genesis 53:510–522, 2015.

Position-Dependent Properties of Limb Cells

An understanding of the way in which cells acquire and utilize positional information in their interactions with one another to generate new pattern, awaits the identification of the molecules that specify positional identity. The vertebrate limb has long been used as an experimental model for the study of pattern formation, and there is currently a considerable body of knowledge about limb development and regeneration at the level of tissues and cells. This information has allowed for the development of a conceptual framework within which to study limbs and from which functional assays for genes involved in pattern formation can be fashioned.

Textual Anatomics: The Mouse Developmental Anatomy Ontology and the Gene Expression Database for Mouse Development (GXD)

The Atlas of Mouse Development has served as a principal reference for mouse anatomists and developmental biologists and has also provided a crucial basis for databases that represent and integrate data relating to developmental anatomy. Using the Atlas as a key reference, an extensive ontology of mouse developmental anatomy has been developed in order to represent the anatomy in a standardized and searchable form. This ontology is being used by the Gene Expression Database for Mouse Development (GXD), the Edinburgh Mouse Atlas and Gene Expression Database (EMAGE), and other resources to record the time and location of gene expression during mouse development. The standardized text-based approach to integrate different types of gene expression information, to place these data into the larger biological context, and to make them thus readily accessible to many types of database searches is a key feature of the GXD. Here we describe the evolution of the mouse developmental anatomy ontology, the current utilities provided by the GXD, as well as broader current and future informatics frameworks for anatomy-based data integration.